2004
DOI: 10.1038/emm.2004.1
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Hypoxia-inducible factor (HIF-1)α: its protein stability and biological functions

Abstract: Hypoxia-inducible factor (HIF-1) is an oxygen-dependent transcriptional activator, which plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and one of three subunits (HIF-1alpha, HIF-2alpha or HIF-3alpha). The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, and phosphorylation. Therefore, HIF-1alpha interacts with several protein factors including … Show more

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Cited by 957 publications
(791 citation statements)
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“…By using cells that are grown under normoxic conditions and the GEF-DN protein that specifically downregulates the Ras activation state, we show that metabolic rerouting does not take place in response to hypoxic conditions, but rather that it is a direct result of oncogenic activation of the Ras pathway. The transcription factor HIF1a, that is directly involved in the positive regulation of glycolytic enzymes in cooperation with Myc (Carmeliet et al, 1998;Osthus et al, 2000;Lee et al, 2004), may be involved in such a Ras-dependent regulation as its mRNA is upregulated in transformed cells (Supplementary Figure S3). While preferential use of the glycolytic pathway may give a selective advantage under hypoxic conditions, it does come at a price.…”
Section: Discussionmentioning
confidence: 99%
“…By using cells that are grown under normoxic conditions and the GEF-DN protein that specifically downregulates the Ras activation state, we show that metabolic rerouting does not take place in response to hypoxic conditions, but rather that it is a direct result of oncogenic activation of the Ras pathway. The transcription factor HIF1a, that is directly involved in the positive regulation of glycolytic enzymes in cooperation with Myc (Carmeliet et al, 1998;Osthus et al, 2000;Lee et al, 2004), may be involved in such a Ras-dependent regulation as its mRNA is upregulated in transformed cells (Supplementary Figure S3). While preferential use of the glycolytic pathway may give a selective advantage under hypoxic conditions, it does come at a price.…”
Section: Discussionmentioning
confidence: 99%
“…This insulin effect is blunted in obese, insulin-resistant Zucker fa/fa rats [4], which represent an animal model of insulin resistance [5]. It is not known whether insulin acts on the VEGF gene directly or via the transcription factor hypoxia-inducible factor-1 (HIF-1), named for its ability to mediate cellular adaptation to oxygen deficiency [6,7].…”
Section: Introductionmentioning
confidence: 99%
“…VEGF is one of its target genes [6,7]. HIF-1 is composed of an α-subunit and a β-subunit [6,7]. HIF-1β is a constitutively expressed nuclear translocator protein which binds HIF-1α and allows it to exert its transcriptional effects, whereas HIF-1α is a cytosolic protein able to translocate to the nucleus where it associates with HIF-1β and binds to a consensus sequence present in the hypoxia response element (HRE) in the promoters of the oxygen-controlled target genes, thus inducing their expression [6,7].…”
Section: Introductionmentioning
confidence: 99%
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